During an inspection of your firm, Express Diagnostics International, Inc., located at 1550 Industrial Drive in Blue Earth, Minnesota, from June 16 through 24, 2014, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures drug of abuse test kits. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.

This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (21 CFR), Part 820. We received a response from Jacqueline Gale, Director of Quality Systems and Regulatory Affairs, dated July 15, 2014, concerning our investigators’ observations noted on the Form FDA 483, List of Inspectional Observations, issued to you on June 24, 2014. We address the response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:

1. Failure to establish adequate procedures for acceptance of in-process product as required by 21 CFR 820.80(c). Specifically, the in-process manufacturing inspection section of Sampling, Testing, and Inspection, WI7.5010, Rev. 02, states that samples of drug test strips are to be tested using controls of (b)(4), and negative control solutions. Documentation Control, SOP4.2001, states that quality system deviations may be used for non-systemic issues on a limited basis as directed by management. Numerous deviations were initiated to allow for acceptance of product without testing with positive controls. For example:

a. Deviation 13-232 was initiated on June 25, 2013, to qualify incoming COC oral fluid cards, lot (b)(4), by negative human donor, negative control solution, and the supplier’s certificate of analysis. No positive control testing was conducted on incoming lot (b)(4). In addition, positive control testing was not performed in-process during manufacturing of lot PC-05305, which included COC oral fluid drug test strip lot (b)(4).

b. Deviations 13-328 and 13-540 were initiated on August 9, 2013, and December 26, 2013, respectively, to release lots PC-08071, PC-08073, and PC-12211 based on negative human donor and negative control solution test data. There was no (b)(4) positive control solution in-process testing for these lots.

c. Deviation 14-003 was initiated on January 13, 2014, to release lot PD-01100 based on negative human donor and negative control solution test data. (b)(4) positive control solution in-process testing was not performed for this lot. The deviation states that positive results will be accepted by incoming test results and the supplier’s certificate of analysis. No positive testing was performed on incoming THC oral fluid strips, lot (b)(4), that later went into finished lot PD-01100.

FDA 483 Response: The response states that CAPAR 14-021 was opened to address in-process testing. It also states that negative and positive controls are being purchased, and testing with these materials was instigated in January. Lastly, the response states that WI7.5010 will be revised. FDA will need to conduct a follow-up inspection to evaluate the adequacy of those reported corrective actions.

2. Failure to establish adequate procedures for corrective and preventive action, which is required by 21 CFR 820.100(a). Specifically:

a. CAPA 12-003 was initiated on January 10, 2012, as a result of an internal audit finding related to management reviews. The action plan, which included “Rewrite all SOP’s for management review…” and “Implement new processes,” was not completed. Management Review, SOP5.6001 Rev. 01, dated October 25, 2011, was not revised. CAPA 12-003 incorrectly states that the action plan was implemented on January 23, 2012. Verification of effectiveness stated that there were no further audit findings on management review output. The CAPA was closed on September 25, 2013.

b. CAPA 13-014 was initiated on October 11, 2013, to address inconsistent performance of lot (b)(4) of THC oral fluid strips. All cards, strips, and finished product were placed in quarantine following confirmation of customer complaints. Verification of effectiveness included monitoring and additional testing of future incoming THC lots. CAPA 13-014 was closed on the same day that it was initiated on October 11, 2013, which was prior to the disposition of the quarantined lots (scrapped during the inspection on June 17, 2014) and before verification of effectiveness activities (performed on February 25, 2014, and March 27, 2014).

c. Following the request of CAPA 10-002 during the inspection, the CAPA file could not be located.

d. For CAPA 11-012, initiated on December 1, 2011, there is no documented progress since February 1, 2012. Similarly, for CAPA 12-013, initiated on April 24, 2012, there is no documented progress since October 30, 2012.

FDA 483 Response: Your response states that CAPAR 14-022 was opened to address the finding. You identified the root cause as personnel not following the SOP.8001 Corrective Action and Preventative Action. The response also stated that CAPAs will be scanned and kept electronically along with a paper copy. Outstanding CAPAs identified during the inspection will be investigated and relevant documents revised where necessary. FDA will need to conduct a follow-up inspection to evaluate the adequacy of those reported corrective actions.

3. Failure to establish adequate procedures for receiving, reviewing, and evaluating complaints as required by 21 CFR 820.198(a). Specifically, Complaint Handling SOP8.3001, Rev. 02, was not implemented to ensure that complaints are processed in a uniform and timely manner [21 CFR 820.198(a)(1)] and investigated where necessary [21 CFR 820.198(b)]. For example:

a. Complaint 13-102 reported false negatives for THC. Investigation of the complaint included testing (b)(4) retain samples, (b)(4) in negative control and (b)(4) in human donor. However, no testing for positive control was conducted.

b. Complaint 13-300 reported that seven out of 25 devices came up positive for THC and three of these were sent to the lab [by the customer] and came back negative. Testing by quality control lab technicians confirmed the potential for false positive results; but raw testing data was not maintained and available for review.

c. Complaint 12-287 reported a discrepancy in the data of a table in the labeling of product. However, an email from the customer also states that they received false negative results for COC; but no complaint was initiated related to the false negative results.

FDA 483 Response: Your response states that CAPAR 14-023 was opened to address the finding. The response also states that SOP8.3001 (Complaint Handling) will be revised and that since 2014 complaints are being handled by the QA/QC department instead of customer service. It was reported that complaints are now being responded to in a thorough and detailed way. FDA will need to conduct a follow-up inspection to evaluate the adequacy of those reported corrections.

4. Failure to establish adequate procedures that define the responsibility for review and the authority for the disposition of non-conforming product, which is required by 21 CFR 820.90(b)(1). Specifically, section 6.7 of Control of Nonconforming Material, SOP8.3002, Rev. 02, states that when the disposition has been completed, the NCR is routed to the Director of QA/RA for close-out. That process was not followed in the following cases:

a. Non-conformances 13-518 and 13-521 were initiated on October 10, 2013, to quarantine finished product within the warehouse due to identified THC strip issues with lot number (b)(4). Non-conformances 13-518 and 13-521 were approved for closure on October 25, 2013, and May 2, 2014, respectively. The lot of quarantined THC strips was not scrapped until June 17, 2014 (during this inspection), approximately eight months after the closure of non-conformance 13-518 and one month after the closure of 13-521.

b. Non-conformance 13-279 was initiated on June 6, 2013, due to BUP failure in negative control. A disposition of “Accept as is” was marked. However, there was no signature approval, and the product has since been used.

FDA 483 Response: Your response states that CAPAR 14-024 was opened to address the findings. Root cause was identified and a revised SOP8.3002 (Control of Nonconforming Material) will be put into place. Relevant personnel will be retrained. FDA will need to conduct a follow-up inspection to evaluate the adequacy of those reported corrections.

5. Failure to establish adequate process control procedures that describe any process controls necessary to ensure conformance to specifications as required by 21 CFR 820.70(a). Specifically, Customer Property and Preservation of Product, SOP7.5005, Rev. 01, states that assembly technicians are assigned a responsibility which may include pre-arrangement or organization, strip insertion, gluing, capping, labeling, pouching, and packing operations. There are no procedures or work instructions established for the following manufacturing operations.

•(b)(4) assembly process

•(b)(4) packaging process

•(b)(4) assembly process

•(b)(4) assembly process

•(b)(4) assembly process

•(b)(4) pouching and packaging processes

FDA 483 Response: Your response states that CAPAR 14-025 was opened to address the findings. The response says that some SOPs have been drafted, and in the coming months all necessary assembly and packaging procedures will be put into place by a cross-functional team of QA/QC and manufacturing. FDA will need to conduct a follow-up inspection to evaluate the adequacy of those reported corrections.

6. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test, which is required by 21 CFR 820.75(a). Specifically, Verification and Validation SOP7.5004, Rev. 01, states that validation is required for all manufacturing procedures that cannot be fully verified by subsequent inspection or test of the final assembly without destroying it.

The (b)(4) Welder, equipment identification (b)(4), is used to weld case halves of the DrugCheck SalivaScan and (b)(4) oral fluid drug tests. Manufacturing parameters, such as (b)(4), vary depending on each product. No documentation was available to establish that this manufacturing process has been validated. Additionally, no inspectional activities of the welding operation are performed.

FDA 483 Response: Your response states that CAPAR 14-026 was opened to address the findings. The response says that the IQ/OQ/PQ for the (b)(4) Welder has been written and will be performed over the next few weeks. FDA will need to conduct a follow-up inspection to evaluate the adequacy of the reported corrections.

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment’s manufacturing and quality assurance systems relative to the requirements of the device Quality System regulation (21 CFR Part 820). You should also submit a copy of the consultant’s report and your certification that you have reviewed the consultant’s report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:

Initial certifications by consultant and establishment – by December 12, 2014

Subsequent certifications of updated audits and corrections – by December 12, 2015, and December 12, 2016.

Please notify this office in writing within 15 working days from the date you receive this letter with an update on the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective actions you have taken. If your planned corrections will occur over time, please include a timetable for implementation. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.

Your response should be sent to Timothy G. Philips, Compliance Officer, at the address on this letterhead. If you have any questions about the content of this letter please contact Mr. Philips at (612) 758-7133.

In addition, we would like to hold a regulatory meeting with you to discuss:

A. Your firm’s practices regarding “Forensic Use Only” labeling. In particular, we are concerned about whether your products have the required premarket clearances for the manner in which they are being promoted and distributed.

We propose the week of September 29 through October 3 for this meeting. The meeting should take about an hour, and it will be held in our office at 250 Marquette Avenue, Suite 600, Minneapolis, Minnesota. As the top official of Express Diagnostics International, Inc. we ask that you attend the meeting. Please telephone Mr. Philips at (612) 758-7133 to schedule the meeting.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483, issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violations and take prompt actions to correct the violations and to bring your products into compliance.